Our research is dedicated to developing and applying novel technologies to understand, harness and engineer the biochemical processing potential of the microbial world. We work at the interface of microbial genomics and biochemistry, synthetic biology and structural biology to study problems with biotechnological and biomedical relevance, with a specific focus on understanding microbial reservoirs of antibiotic resistance and engineering microbial catalysis of plant biomass into value chemicals.

Microbial Reservoirs of Antibiotic Resistance. The rapid and unrelenting proliferation of multiple antibiotic resistance in virtually all clinically-relevant human pathogens is compromising our ability to treat infectious disease. Since antibiotic resistance determinants encoded on mobilizable elements can readily transfer between diverse bacteria, we are interested in understanding the relative abundance and diversity of reservoirs of resistance genes encoded within microbial communities from different environments and their accessibility to clinically relevant pathogens. We use high-throughput phenotypic assays to identify and compare the resistance profiles of bacteria inhabiting a variety of soil and marine habitats, as well as the bodies of humans and other animals. An intriguing community under investigation is a recently discovered set of phylogenetically diverse soil bacteria with the capacity to consume many antibiotics as their sole source of carbon. These bacteria are also resistant to multiple antibiotics at extremely high concentrations, and are closely related to many human pathogens, highlighting their potential role as a relevant and previously unappreciated reservoir of clinically-relevant resistance machinery. We are using culturing independent metagenomic selections, transposon mutagenesis, whole genome sequencing, and a battery of biochemical and structural methods to characterize antibiotic metabolism and resistance machinery at the molecular level. One of our long-term goals is to develop methods to curb the accessibility of this machinery to pathogens.

Engineering microbial catalysts for converting biomass to value chemicals. Global environmental problems related to the combustion of fossil fuels and increasing concerns about their supply underscore the importance of developing renewable fuel alternatives with a reduced environmental footprint. The application of synthetic biology to engineer microbial biocatalysts that produce biofuels from diverse lignocellulosic materials including waste and low agricultural intensity biomass holds promise to deliver one such sustainable alternative. Since plant biomass is naturally microbially recycled in the environment, our research is focused on harnessing the reservoir of enzymatic machinery encoded by soil microbial communities that allows for the tolerance and complete processing of its constituent chemicals. We use both culture based as well as culture independent functional metagenomic approaches to discover and transfer such processing machinery into candidate biofuel producing strains. In this context, we are focused on improving the yields and efficiencies of metagenomic library construction and expression, and design and application of appropriate functional selections for chemical utilization, tolerance and production of biofuel chemicals from plant biomass. We will also apply high-resolution experimental and computational methods to elucidate and redesign the molecular structures and functions of gene products whose exact functional antecedents cannot be inferred by their sequence alone, as well as enzymes with sub-optimal activities.